Assessment of quality of life determinants in hemodialysis patients of a developing country: A cross-sectional study during ongoing COVID-19 pandemic

Background and Objectives: Patients of end-stage renal disease are prone to have a very low quality of life (QoL). Variety of factors influence the QoL among sufferers of chronic kidney disease comprising of type of dialysis, sufficiency/adequacy of dialysis, and associated burden of disease. We conducted this study amidst the pandemic to determine the associated factors for poor QoL in hemodialysis patients during the ongoing pandemic. Patients and Methods: This cross-sectional study was conducted in a hemodialysis unit of a tertiary care hospital. A total of 118 participants responded to the validated questionnaire of Quality of Life Index-dialysis version-III (QLI). Higher scores signify good QoL, total scores are further categorized into subgroups desirable, relatively desirable and undesirable. Results: The mean age of the participants was 57.36 ± 10.03 years and mean body mass index of 26.73 ± 5.54 kg/m2. The mean total QoL of the study population was found quite low (12.99 ± 5.89). Majority of respondents fell in undesirable category of QoL (49.2%). Total QoL (P = 0.004) and subscale health/functioning (P = 0.003) were significantly lower in females. All the subscales along with total QoL scores were found lower in twice-weekly dialyzed patients (P < 0.001). Marital status (P = 0.049) and twice-weekly dialysis (P < 0.001) were found significant with undesirable QoL. On multivariate analysis, significant determinants of undesirable QoL were twice-weekly dialysis (P = 0.001), catheter access (P = 0.034), phosphate (P = 0.005) and uric acid (P = 0.006). Conclusion: Inadequate dialysis due to lesser frequency per week leading to poorly cleared toxic substances were most significant contributors of poor QoL in our study.


Introduction
Hemodialysis is preferably opted modality of treatment for survival by more than 70% of patients with end-stage renal disease (ESRD). [1,2] Chronic kidney disease (CKD) imparts a pronounced negative effect on quality of life (QoL) of sufferers prominently due to association with impairment and restrictions in all aspects of daily life. [1,3] Patients with ESRD are prone to have very low QoL. [4] Variety of factors influence the QoL among sufferers of CKD undergoing hemodialysis comprising of type of dialysis (hemodialysis and peritoneal dialysis), sufficiency of dialysis, daily dialysis, night shift of dialysis, depression and anxiety associated with burden of disease, frequent hospital admissions, three times a Medicine week visits to dialysis centers, decline in physical fitness and increasing age. [5,6] QoL in patients of ESRD undergoing dialysis is also affected by multiple clinical manifestations (i.e., vomiting, nausea, decreased appetite, exhaustion, muscle cramps, chronic pain, and sleep disturbances). [1,2] Pakistan has a predicted number of 150 patients with CKD per annum per million, with estimated value of 16,000 patients each year. [5] Sufferers of ESRD initially are scheduled thrice weekly irrespective of residual renal status. [7] The frequent sessions of dialysis exert prominent effect on QoL. [8] Maximum population of United States of America (USA), Europe, and Japan undergo a traditional thrice weekly course of dialysis while patients of Thailand undergo twiceweekly course of dialysis due to economic restrictions, curtail the decline of QoL. [8] A thrice-weekly plan of dialysis ensures the prolong duration of treatment and higher Kt/V were associated with decline in rate of mortalities due to adequate dialysis. [8] Hemodialysis patients from Taiwan showed lower scores of QoL when compared with patients undergoing peritoneal dialysis. [9] The reported quality of life using the same scale in our study was reported to be satisfactory in the Michigan population on peritoneal dialysis. [10] Hence, QoL is significantly more of a concern in hemodialysis patients. A study demonstrates empowerment counseling sessions of hemodialysis patients improve self-efficacy, quality of life, and clinical status. [11] On the contrary, currently, newer therapies are employed amidst the pandemic and compared with hemodialysis, QoL generally appears to be superior with convective therapies. [12][13][14] In 1 randomized controlled trial conducted in the Netherlands, QoL improved on hemofiltration versus low-flux hemodialysis. [12] In a meta-analysis, QoL significantly improved using an unvalidated scale in patients on hemodiafiltration therapy compared with those on hemodialysis therapy. [15] Hence, we conducted this study to determine the associated factors for poor QoL in hemodialysis patients during the coronavirus disease 2019 (COVID-19) ongoing pandemic. The secondary aim of this study is to associate biochemical markers with QoL among sufferers of ESRD undergoing either twice weekly or thrice weekly sessions of dialysis.

Study design and settings
This observational study was conducted during the ongoing COVID-19 pandemic as cross-sectional analysis in a hemodialysis unit of a tertiary care hospital during the months of May till October 2021.
Participants and variables: More than 200 patients are registered for hemodialysis in the unit. After taking ethical approval from the institutional review board, assessment of QoL by using the Ferrans and Powers Quality of Life Index-dialysis version-III (QLI) was undertaken with consent of the participants. [16][17][18] The second part of the questionnaire was recording patient factors and biochemical data of the patients including age, body mass index (BMI), duration of hemodialysis onset, frequency of dialysis per week, marital status, comorbidities, line access [Arteriovenous (AV) fistula or catheter], and current laboratory values of hemoglobin, albumin, uric acid, serum phosphate, serum calcium, and parathyroid hormone (PTH) levels. The most recent laboratory markers were considered for preceding 1 month prior to inclusion in the study.

Bias
Some questions also depend on patients' perception regarding certain beliefs; hence they might affect the results.

Study size
A sample size of 132 was calculated via OpenEpi sample size calculator, [22] in which we used 5% as a margin of error, 95% as confidence interval (CI), 200 as population size (currently enrolled number of patients in hemodialysis unit) and anticipated frequency of outcome factor in the population of 50%. Hence, the questionnaire was made available in printed form with translation in local language alongside for better understanding. At least, 180 patients were approached for filling out the responses, out of which 137 agreed to participate giving a response rate of 76.1%. A total of 19 questionnaires were excluded due to incomplete responses. Hence, a total of 118 respondents (participants) were recruited in the analysis.

Statistical methods
Subsequently, data were tabulated, coded then analyzed using the computer program for Windows IBM SPSS (Statistical Package for Social Sciences) version 25.0, Armonk, NY: IBM Corporation.

Quantitative variables
Descriptive statistics were calculated in the form of mean ± standard deviation, 95% CI, range, median and interquartile range (IQR) and frequency (percentage). In the statistical comparison between the different groups, the significance of difference was tested using either Mann-Whitney used to compare between different groups of nonparametric data and

What Was Known/What This Study Adds
What Was Known • Patients of end-stage renal disease (ESRD) are prone to have a very low quality of life (QoL). • Variety of factors influence the QoL among sufferers of CKD. • Hemodialysis is also recognized with affecting the quality of life and sleep in patients along with the chronic kidney disease itself.

What This Study Adds
• Lesser frequency of dialysis/inadequate dialysis was found the most significant contributor towards poor QoL. • Certain biochemical markers were the major contributor towards poor QoL like uric acid, serum phosphate and others. • Obtaining constant COVID-19 updates and fear of contracting the virus were additional associated factors on multivariate analysis.
inter-group comparison of categorical data was performed by using Pearson chi-square test or Fisher exact test as indicated. Multivariate linear regression was conducted for only the continuous descriptive variables reported unstandardized and standardized coefficients, while multivariate regression analysis was conducted for all the qualitative variables. Crude odds ratio (OR) and adjusted odds ratio (AOR) were reported subsequently. A P value <0.05 was considered statistically significant.

Sociodemographic characteristics of participants
A total of 118 responses were including in the analysis having a mean age of 57.36 ± 10.03 years and mean BMI of 26.73 ± 5.54 kg/ m 2 . About 48.3% of participants were enrolled for twice-weekly dialysis and rest 51.7% for thrice weekly, majority dialyzed via AV fistula access (79.7%). Around 55.1% comprised of men, 66.9% were married, 74.6% hypertensive, 56.8% diabetic, and 11.9% suffered from ischemic heart disease (IHD). The mean values of all laboratory markers are shown in Table 1.
With respect to diabetes, hypertension and IHD, no such differences were observed. Among categorization, marital status (P = 0.049) and frequency of dialysis (P < 0.001) were found significant, as shown in Figures 3 and 4

Outcome data and main results
All the descriptive variables were analyzed for multiple linear regression with QoL score (total) as dependent variable. Increased age was inversely related to QoL score (P = 0.031), while uric acid levels (P < 0.001), serum phosphate (P = 0.044) and BMI (P < 0.001) were directly associated with QoL score as shown in  Table 4. Table 1 Baseline data of the study population (n = 118).

Characteristics
Frequency/descriptive

Discussion
Many factors related to QoL of hemodialysis patients were found in the literature. Starting with perceived social support, Iranian population showed direct correlation of this factor with the same index of QoL used in our study in all the subgroups. [23] Poor nocturnal quality sleep and increased daytime sleepiness are associated with decreased quality of life in hemodialysis patients of USA. [24] Data from United Arab Emirates (UAE) suggested lower educational level and presence of chronic illness had the strongest impact on poor QoL. [25] Hemodialysis patients from Saudi Arabia showed higher QoL scores in those undergoing afternoon shift dialysis; furthermore, male gender, employed patients, and nondiabetics also showed higher scores. [26] Data from Bahrain suggested educational level, urban residence, and marital status determine poor QoL. [27] Only age and educational level had a negative impact on quality of life of Iranian population on hemodialysis with either hepatitis B, or C seropositivity. [28] A systematic review from Iran also suggested similar findings when compared with normal population and other chronic illnesses like diabetes and cardiac disease. [29] Since frequency of dialysis was the major factor contributing to poor QoL in our patients, most of the comparisons drawn from the other studies revolve around this factor. The frequency of hemodialysis sessions has a vital role in the survival and prevalence of complications in patients enduring ESRD. [30] Abundant studies conducted regarding frequency of twice or thrice sessions a week in sufferers of CKD reported age range of 50-60 years in maximum individuals. [8,[30][31][32][33] No gender discrimination was observed in encountering CKD among both genders, while in terms of sessions of dialysis, increased frequency of twiceweekly dialysis was detected among females. [8,[30][31][32][33] Significant frequency of thrice-weekly dialysis was reported in males. [8] Primary causes of CKD were diabetes mellitus and glomerulonephritis in multiple studies. [7,30,32,33] Significant prevalence of cardiovascular diseases, stroke, dementia, hemiplegia, chronic pulmonary diseases were detected in patients of CKD undergoing 3 sessions of dialysis per week in numerous studies, [30][31][32] while no difference regarding comorbidities was reported by a trivial study. [33] Higher glomerular filtration rate (GFR), urine output, and decreased creatinine levels were observed in sufferers undergoing thrice-weekly dialysis in study regulated by Park et al [7] On contrary, study regulated within population of USA reported lower serum creatinine levels in individuals opting for twiceweekly sessions of dialysis when compared with thrice-weekly sessions. [32] Thaweethamcharoen et al, reported no difference in creatinine levels. [8] Hanson et al, reported decreased creatinine levels and elevated levels of albumin as distinctive features encountered in individuals undergoing twice-weekly sessions of dialysis. [32] According to the Chinese renal data system, inhabitants of China suffering from ESRD undergo twice-weekly sessions of dialysis, factors leading to this management plan are patient comorbidities, residual function status, desire of gradual initiation of dialysis and insurance status. [31] Previous studies regulated in a similar pattern concluded that twice-weekly sessions of dialysis were utilized for patients of old age, females, sufferers with low BMI and patients with residual renal function at initiation of renal replacement therapy on contrast this regimen is not recommended recently by international guidelines or in sufferers with urea clearance of <2 ml/min. [32,34] Multiple studies documented the comparison of clinical outcomes between fewer weekly sessions of dialysis versus thrice-weekly plan of dialysis concluding that fewer consecutive sessions of dialysis favor the conservation of residual renal function and do not result in decline of QoL and patient survival. [7] Lower clearance rate, increased Kt/V, elevated blood urea nitrogen levels (BUN), PTH and phosphate levels while decreased levels of calcium were detected in patients settling for twice-weekly program of dialysis in a study conducted within inhabitants of China and Thailand. [8,31] Anemia was prominently suffered by patients with increased frequency of thrice-weekly sessions of dialysis, [30] while no statistically significant difference was observed in another study conducted in similar fashion. [8] Twice-weekly sessions of dialysis were popular among older Caucasian women and individuals suffering from Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) according to study mentioned above. [32] Majority of studies stated better QoL among individuals adjusting with twice-weekly sessions of dialysis as compared to thrice-weekly sessions, [2,7,30,33] while a study recorded no difference of QoL among both frequencies of dialysis. [8,31] Impaired mental status, disturbances of sleep, decline in sexual and cognitive function was prominent among patients with thrice-weekly schedule of dialysis. [7] Social interaction and support were prevalent within individuals with twice-weekly sessions of dialysis. [2,7] Decline in mortality rate was observed in patients with twice-weekly sessions of dialysis, [32] while prevalence of infection was high among patients with thrice-weekly sessions of dialysis. [33] No difference within BMI, nutritional status and weight in association with frequency of dialysis was detected in patients of CKD. [7,33] Other significant factors contributing to improved QoL in hemodialysis patients were illness acceptance and enough disease knowledge. [1,35] Data from Ethiopia suggested socioeconomic and educational status on top of higher hemoglobin levels were significant determinants for improved QoL. [2] Higher BMI and duration of dialysis onset >5 years were associated with poor QoL in an Iranian population; however, these variables are insignificant in our findings. [35] Previous studies from Pakistan have suggested presence of diabetes and duration of dialysis onset negatively correlating with QoL. [5] But no association was found in frequency of dialysis per week with QoL in their study participants contrary to our findings. Data from Poland suggested female gender, elderly age and fatigue during dialysis were profound determinants for poor QoL, [6] as opposed to socioeconomic and educational well-being for good QoL. [3,6] A randomized trial from China rendered twice-weekly dialysis more favorable toward quality of life with certain socioeconomic and social support factors related to it, thus opposing our results, [30] while a study from India suggested equal effects of twice and thrice-weekly dialysis on QoL. [33] In another study, less frequent dialysis sessions per week have a higher score of QoL on physical and mental scales than more frequent sessions, again contradicting our results. [2] More recently, COVID-19 pandemic has also affected the QoL of hemodialysis patients as evident by our results; however, not much literature is available on it to compare our results.

Limitations
There were some limitations of the current study. The study sample was not that adequate to represent a larger hemodialysis population, but a convenience sample from a single institution. The study was cross-sectional hence not signifying the causal relationship between the factor variables and QoL. Finally, because the data was collected during the dialysis unit visits accompanying by their family members, influence of those family members in answering the questions of the participants could not be certainly ruled out. Some questions also depend on patients' perception regarding certain beliefs; hence they might affect the results. The strengths of the study were validated tools utilized, and inclusion of biochemical parameters in the analysis which are usually not a part of such surveys while reporting QoL in hemodialysis patients.

Conclusions
Our study concluded many determinants associated with relatively desirable and undesirable QoL using a validated index. Certain biochemical markers were the major contributor towards poor QoL, which can be asserted to the fact these molecules are poorly cleared from the bloodstreams by various factors including poor compliance to dialysis or lesser Kt/V. Hence, lesser frequency of dialysis implying to inadequate dialysis was found the most significant contributor towards poor QoL in our study population.